PMID- 37111463
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230501
IS  - 2076-0817 (Print)
IS  - 2076-0817 (Electronic)
IS  - 2076-0817 (Linking)
VI  - 12
IP  - 4
DP  - 2023 Apr 9
TI  - NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially 
      Expressed in Respiratory-Syncytial-Virus- and Rhinovirus-Infected Hospitalized 
      Children.
LID - 10.3390/pathogens12040577 [doi]
LID - 577
AB  - Respiratory diseases caused by respiratory syncytial virus (RSV) and human 
      rhinovirus (HRV) are frequent causes of the hospitalization of children; 
      nonetheless, RSV is responsible for the most severe and life-threatening 
      illnesses. Viral infection triggers an inflammatory response, activating 
      interferon (IFN)-mediated responses, including IFN-stimulated genes (ISG) 
      expression with antiviral and immunomodulatory activities. In parallel, the 
      reactive oxygen species (ROS) production activates nuclear factor erythroid 
      2-related factor 2 (NRF2), whose antioxidant activity can reduce inflammation by 
      interacting with the NF-kB pathway and the IFN response. To clarify how the 
      interplay of IFN and NRF2 may impact on clinical severity, we enrolled children 
      hospitalized for bronchiolitis and pneumonia, and measured gene expression of 
      type-I and III IFNs, of several ISGs, of NRF2 and antioxidant-related genes, 
      i.e., glucose-6-phosphate dehydrogenase (G6PD), heme oxygenase 1 (HO1), and 
      NAD(P)H dehydrogenase [Quinone] 1 (NQO1) in RSV- (RSV-A N = 33 and RSV-B N = 30) 
      and HRV (N = 22)-positive respiratory samples. NRF2 and HO1 expression is 
      significantly elevated in children with HRV infection compared to RSV (p = 0.012 
      and p = 0.007, respectively), whereas ISG15 and ISG56 expression is higher in 
      RSV-infected children (p = 0.016 and p = 0.049, respectively). Children admitted 
      to a pediatric intensive care unit (PICU) had reduced NRF2 expression (p = 
      0.002). These data suggest, for the first time, that lower activation of the NRF2 
      antioxidant response in RSV-infected infants may contribute to bronchiolitis 
      severity.
FAU - Sorrentino, Leonardo
AU  - Sorrentino L
AUID- ORCID: 0000-0003-3804-2946
AD  - Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 
      00185 Rome, Italy.
FAU - Toscanelli, Walter
AU  - Toscanelli W
AUID- ORCID: 0000-0001-9212-4972
AD  - Department of Public Health and Infectious Diseases, Laboratory Affiliated to 
      Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 
      Rome, Italy.
FAU - Fracella, Matteo
AU  - Fracella M
AUID- ORCID: 0000-0002-2885-2382
AD  - Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 
      00185 Rome, Italy.
FAU - De Angelis, Marta
AU  - De Angelis M
AUID- ORCID: 0000-0002-1916-6508
AD  - Department of Public Health and Infectious Diseases, Laboratory Affiliated to 
      Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 
      Rome, Italy.
FAU - Frasca, Federica
AU  - Frasca F
AD  - Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 
      00185 Rome, Italy.
FAU - Scagnolari, Carolina
AU  - Scagnolari C
AUID- ORCID: 0000-0003-1044-1478
AD  - Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 
      00185 Rome, Italy.
FAU - Petrarca, Laura
AU  - Petrarca L
AD  - Department of Maternal Infantile and Urological Sciences, Sapienza University, 
      00185 Rome, Italy.
FAU - Nenna, Raffaella
AU  - Nenna R
AUID- ORCID: 0000-0001-8880-3462
AD  - Department of Maternal Infantile and Urological Sciences, Sapienza University, 
      00185 Rome, Italy.
FAU - Midulla, Fabio
AU  - Midulla F
AD  - Department of Maternal Infantile and Urological Sciences, Sapienza University, 
      00185 Rome, Italy.
FAU - Palamara, Anna Teresa
AU  - Palamara AT
AUID- ORCID: 0000-0001-8330-4381
AD  - Department of Public Health and Infectious Diseases, Laboratory Affiliated to 
      Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 
      Rome, Italy.
AD  - Department of Infectious Diseases, Istituto Superiore di Sanita, 00161 Rome, 
      Italy.
FAU - Nencioni, Lucia
AU  - Nencioni L
AUID- ORCID: 0000-0003-4427-4823
AD  - Department of Public Health and Infectious Diseases, Laboratory Affiliated to 
      Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 
      Rome, Italy.
FAU - Pierangeli, Alessandra
AU  - Pierangeli A
AUID- ORCID: 0000-0003-0633-360X
AD  - Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 
      00185 Rome, Italy.
LA  - eng
GR  - EU funding within the NextGeneration EU-MUR PNRR Extended Partnership initiative 
      on Emerging Infectious Diseases (Project n. PE00000007, INF-ACT)/European Union/
GR  - PRIN 2020: B89J21033130001/Italian Ministry of University and Research MUR/
PT  - Journal Article
DEP - 20230409
PL  - Switzerland
TA  - Pathogens
JT  - Pathogens (Basel, Switzerland)
JID - 101596317
PMC - PMC10144743
OTO - NOTNLM
OT  - NRF2
OT  - antioxidant response
OT  - human rhinovirus
OT  - interferon
OT  - respiratory syncytial virus
COIS- The authors declare no conflict of interest.
EDAT- 2023/04/28 06:42
MHDA- 2023/04/28 06:43
PMCR- 2023/04/09
CRDT- 2023/04/28 01:46
PHST- 2023/03/03 00:00 [received]
PHST- 2023/03/23 00:00 [revised]
PHST- 2023/03/24 00:00 [accepted]
PHST- 2023/04/28 06:43 [medline]
PHST- 2023/04/28 06:42 [pubmed]
PHST- 2023/04/28 01:46 [entrez]
PHST- 2023/04/09 00:00 [pmc-release]
AID - pathogens12040577 [pii]
AID - pathogens-12-00577 [pii]
AID - 10.3390/pathogens12040577 [doi]
PST - epublish
SO  - Pathogens. 2023 Apr 9;12(4):577. doi: 10.3390/pathogens12040577.